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Poly-specific neoantigen-targeted cancer vaccines delay patient derived tumor growth
Luigi Aurisicchio1,2,3, Erika Salvatori1, Lucia Lione1,4
1Takis, Rome, Italy.
Background:
Personalized cancer vaccines based on neoantigens have reached the clinical trial stage in melanoma. Different vaccination protocols showed efficacy in preclinical models without a clear indication of the quality and the number of neoantigens required for an effective cancer vaccine.
Methods:
In an effort to develop potent and efficacious neoantigen-based vaccines, we have developed different neoantigen minigene (NAM) vaccine vectors to determine the rules for a successful neoantigen cancer vaccine (NCV) delivered by plasmid DNA and electroporation. Immune responses were analyzed at the level of single neoantigen by flow cytometry and correlated with tumor growth. Adoptive T cell transfer, from HLA-2.1.1 mice, was used to demonstrate the efficacy of the NCV pipeline against human-derived tumors.
Results:
In agreement with previous bodies of evidence, immunogenicity was driven by predicted affinity. A strong poly-functional and poly-specific immune response was observed with high affinity neoantigens. However, only a high poly-specific vaccine vector was able to completely protect mice from subsequent tumor challenge. More importantly, this pipeline - from the selection of neoantigens to vaccine design - applied to a new model of patient derived tumor xenograft resulted in therapeutic treatment.
Conclusions:
These results suggest a feasible strategy for a neoantigen cancer vaccine that is simple and applicable for clinical developments.
Insights
Developing effective personalized cancer vaccines requires understanding neoantigen quality. This study identified high-affinity, poly-specific neoantigen vaccines as crucial for complete tumor protection and therapeutic success.
Area of Science:
- Oncology
- Immunology
- Vaccine Development
Background:
- Personalized cancer vaccines targeting neoantigens are in clinical trials for melanoma.
- Preclinical models show vaccine efficacy, but optimal neoantigen number and quality remain unclear.
Purpose of the Study:
- To establish rules for effective neoantigen cancer vaccines (NCVs).
- To develop potent neoantigen minigene (NAM) vaccine vectors for DNA delivery and electroporation.
Main Methods:
- Immune responses to single neoantigens were analyzed via flow cytometry.
- Correlated immune responses with tumor growth in mice.
- Utilized adoptive T cell transfer to test NCV efficacy against human tumors.
Main Results:
- Neoantigen immunogenicity correlated with predicted binding affinity.
- High-affinity neoantigens induced strong poly-functional and poly-specific immune responses.
- Only high poly-specific vaccine vectors provided complete protection against tumor challenge.
- The NCV pipeline demonstrated therapeutic efficacy in patient-derived tumor xenografts.
Conclusions:
- A feasible, simple strategy for neoantigen cancer vaccines is proposed.
- This approach is applicable for clinical development.
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